Short-term outcome and attainment of secondary prevention goals in patients with acute coronary syndrome--results from the countrywide TARGET study.

BACKGROUND/OBJECTIVES: Acute coronary syndromes (ACS) continue to pose a significant medical and socioeconomic burden worldwide. Optimal management strategy aims to improve short and long-term outcome. The present study aims to assess short-term outcome of real-world ACS patients and evaluate the achievement rate of secondary prevention goals. METHODS: The TARGET study is an observational study enrolling 418 consecutive ACS patients from 17 centers countrywide (78.0% males, 63.9 ± 12.9 years). After the in-hospital phase, patients were followed for 6 months. In total, 366 patients were included in the prospective phase of the study. At the end of the follow-up, mortality, major adverse cardiovascular events (MACE), prescription pattern of cardiovascular medications, lipid levels, adherence rate to treatment and behavioral recommendations were measured. RESULTS: The overall mortality was 4.8% and the rate of MACE was 17.5%. At 6 months, a significantly lower proportion of patients received antiplatelet agents and statins as compared to hospital discharge. At the end of the follow-up, 87.7% of patients remained on statin treatment, yet only 18.2% of patients had LDL cholesterol levels less than 70 mg/dL. The adherence pattern to lifestyle and dietary recommendations remained low (66.2% quit smoking, 55.8% and 81.3% followed physical activity and dietary recommendations respectively). CONCLUSION: Despite the low rate of mortality and MACE occurrence rate in this countrywide observational study, the attainment rate of secondary prevention goals is relatively poor. Improvement interventions focusing in these gaps of optimal care provision are expected to have a favorable impact on the prognosis of real world ACS patients.

Temporal and spatial distribution of ST-elevation myocardial infarction admissions in a countrywide registry.

BACKGROUND: Current guidelines propose different reperfusion strategies for ST-elevation myocardial infarction (STEMI) depending on the time delay from pain onset, the availability of a catheterization laboratory and the patient's characteristics. In order to implement national strategies to improve reperfusion rates the existing situation must be first analysed. The aim of this report is to provide a description of where and when STEMI patients present in a countrywide registry. METHODS: The Hellenic Infarction Observation Study (HELIOS) was a countrywide registry that enrolled 1096 patients with STEMI from 31 hospitals with a proportional representation of all types of hospitals from all geographical areas. We recorded the proportion of patients that fits within each category of treatment algorithms. RESULTS: The following percentages of the total STEMI population were recorded: a) admitted in invasive hospitals within 12 h 28.7% (with 26% of those not reperfused) and after 12 h 5.9% and b) admitted in non-invasive hospitals within 3 h 34.9% (with 30% of those not reperfused), 3-12 h 19.3% and after 12 h 11%. CONCLUSIONS: A large proportion of STEMI patients are admitted either in an invasive hospital within 12 h or in a non-invasive one within 3 h from pain onset and therefore can be treated locally according to the guidelines. A relatively small percentage of patients are late presenters in non-invasive centres and are candidates for immediate transfer for primary PCI. These data could be useful in planning reperfusion strategies at countrywide level since not all patients may require immediate transfer for primary PCI.

In-hospital mortality of habitual cigarette smokers after acute myocardial infarction; the "smoker's paradox" in a countrywide study.

AIMS: Habitual cigarette smokers, paradoxically, present improved short-term prognosis after acute myocardial infarction, a phenomenon often termed "smoker's paradox". We sought to examine cigarette smokers' post-infarction survival advantage in a countrywide survey of unselected, consecutive patients presenting with acute myocardial infarction. METHODS AND RESULTS: The study population was derived from the registry of the Hellenic study of acute myocardial infarction, which recruited 7433 consecutive patients with acute myocardial infarction from 76, out of a total of 86, hospitals countrywide. Cigarette smokers presented with lower unadjusted mortality rates (7.4% vs 14.5%, P<0.001), were younger, predominantly of male gender and were less likely to suffer from diabetes mellitus and arterial hypertension. When all univariate predictors of poor outcome were included as covariates in multivariate analysis, smoking status was not significantly associated with inhospital mortality (relative risk=1.12, 95% CI=0.86-1.44, P=0.399). The beneficial effect of thrombolytic therapy was independent of the smoking status in both univariate and multivariate analysis. CONCLUSION: Unadjusted mortality rates are significantly lower in smokers, but age accounted for much of their seemingly improved outcome. When a number of additional clinical variables were taken into consideration, no significant influence of habitual smoking on early outcome following acute myocardial infarction was observed.

Evolutionary pattern and prognostic importance of heart rate variability during the early phase of acute myocardial infarction.

AIMS: To investigate the evolution of time domain heart rate variability in the early phase of acute myocardial infarction (MI) and assess its prognostic ability. METHODS: We analysed several measures of heart rate variability (SDNN, SDANN, SDNN index, RMSSD) in 138 patients at days 0, 1 and 5+/-1 after hospital admission for acute MI. Results were correlated with infarct site, clinical variation and clinical outcome (death, MI, PTCA, CABG surgery). RESULTS: Measures of heart rate variability (SDNN, SDANN and SDNN index) declined during the first 24 h after acute MI (P<0.01) and increased to admission levels after about 5 days. SDNN values on day 0, 1 and 5 respectively were: 86+/-35, 75+/-28 and 87+/-27 ms. Patients with anterior infarction had lower heart rate variability than patients with inferior infarction on all test days but similar evolution patterns. After 3 years of follow-up there were 12 cardiac deaths (8.7%) and six resuscitated arrests and 33 (24%) new MIs, or revascularisation procedures. The evolutionary pattern of heart rate variability was similar in survivors to those who died although values were generally lower. Mortality was significantly higher in the group with SDNN<50 ms at day 1 (P<0.01) and 5 (P<0.05), but not at day 0. CONCLUSIONS: Our findings show that autonomic imbalance, already evident on the day of the acute event, progresses further over the next 24 h and recovers over the next few days. Low heart rate variability as early as 24 h after acute MI may be a useful predictor of cardiac mortality and contribute to the early risk stratification and therapeutic management of patients.

Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.

The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Low doses of scopolamine increase cardiac vagal tone in the acute phase of myocardial infarction.

BACKGROUND: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI. METHODS AND RESULTS: Patients were randomized to a scopolamine (n = 17) or a placebo patch (n = 19) in a double-blind fashion 4.20 +/- 0.18 days after acute MI. Cardiac vagal activity was assessed by testing the arterial baroreflex sensitivity (BRS) using the phenylephrine method and by power spectral analysis of the RR interval variability. Twenty-four hours after scopolamine, we found a significant increase in BRS (from 7.05 +/- 1.21 to 13.99 +/- 2.33 ms/mm Hg, P < .05) and in RR variability, expressed as the mean standard deviation of 512 normal consecutive RR intervals (from 18.09 +/- 2.64 to 31.16 +/- 4.16 milliseconds, P < .05). The amplitude of respiratory sinus arrhythmia, measured by the absolute power of the high-frequency spectral component, was also enhanced (from 62.55 +/- 21.49 to 305.33 +/- 95.68 milliseconds squared, P < .05), whereas the power in the low-frequency spectral component of the RR variability, which results from the interaction between cardiac sympathetic and vagal activity, did not change significantly (from 73.12 +/- 24.44 to 126.46 +/- 44.29 milliseconds squared, P = .93). CONCLUSIONS: In patients in the acute phase of MI, low doses of scopolamine cause a sustained increase in cardiac vagal tone and improve the autonomic indices associated with mortality.

Hemodynamic effects of captopril and isosorbide mononitrate started early in acute myocardial infarction: a randomized placebo-controlled study.

OBJECTIVES: The aim of this study was to study the hemodynamic effects of orally administered captopril and isosorbide mononitrate in suspected acute myocardial infarction. BACKGROUND: Early treatment with converting enzyme inhibitors and nitrates in acute myocardial infarction may limit infarct expansion and prevent left ventricular dilation. METHODS: In a double-blind study, 81 patients were randomized within 36 h of the onset of symptoms of suspected acute myocardial infarction to 1 month of oral captopril (6.25 mg initial dose, followed 2 h later by 12.5 mg and continuing with 12.5 mg three times daily), isosorbide mononitrate (initial dose 20 mg followed by 20 mg three times daily) or matching placebo. The effects of treatment on changes from baseline in mean arterial blood pressure, heart rate, stroke volume, cardiac output and systemic vascular resistance were assessed noninvasively using Doppler echocardiography 1 h after the first dose, 1 week after infarction and at 6 weeks (that is, 2 weeks after the scheduled end of trial treatment). RESULTS: One hour after the start of treatment, blood pressure was reduced by approximately 10% with both captopril and isosorbide mononitrate, but this difference did not persist at 1 week. Captopril was associated with a significant increase in cardiac output compared with placebo of 13 +/- 3% at 1 h (p < 0.01), 23 +/- 5% at 1 week (p < 0.001) and 22 +/- 6% (p < 0.05) at 6 weeks (2 weeks after the end of trial treatment). This increase in cardiac output with captopril was mainly due to a substantial and sustained increase in stroke volume, although there was also a small increase in heart rate at 1 week. Both captopril and isosorbide mononitrate reduced systemic vascular resistance within 1 h of the start of treatment, but only the effect of captopril was sustained (perhaps because the three-times daily nitrate regimen induced tolerance). Study treatment was well tolerated, and the incidence of withdrawal of study treatment for hypotension was not significantly different from that with placebo. CONCLUSIONS: This study indicates that the hemodynamic effects of both captopril and isosorbide mononitrate are well tolerated in the acute phase of myocardial infarction and that captopril favorably influences cardiac function.

Effects on ventricular arrhythmias of oral captopril and of oral mononitrate started early in acute myocardial infarction: results of a randomised placebo controlled trial.

OBJECTIVE: To assess the effects of oral vasodilator treatment on ventricular arrhythmias in acute myocardial infarction. SETTING: Coronary care units at the John Radcliffe Hospital, Oxford, and the Royal Infirmary, Edinburgh. PATIENTS: 100 patients with suspected acute myocardial infarction entered the study at a mean of 13 hours from symptom onset. DESIGN OF INTERVENTION: Double blind randomisation to 4 weeks treatment with captopril (12.5 mg three times a day after a 6.25 mg test dose (n = 32)) or isosorbide mononitrate (20 mg three times a day (n = 31)) or placebo control (n = 37). OUTCOME MEASURES: Ventricular arrhythmic events assessed by 48 hours of Holter monitoring starting at the time of randomisation. RESULTS: The number of ventricular extrasystoles/hour for captopril, mononitrate, and placebo was respectively (median and range) 6 (0-162), 4 (0-38), and 10 (0-932) (2p < 0.02 mononitrate v placebo). The number of episodes of multiple extrasystoles/hour was 0.2 (0-22), 0.3 (0-4), and 0.5 (0-19); (2p < 0.02 mononitrate v placebo). Episodes of ventricular tachycardia showed a non-significant decrease in the captopril and mononitrate groups (mean (SEM) 3.2 (0.8), 2.4 (0.7), and 4.7 (1.3) for the 48 hour period). The incidence of idioventricular rhythm was also reduced in both active treatment groups (28%, 19%, and 46% (2p < 0.05 mononitrate v placebo)). CONCLUSIONS: Oral mononitrate (and perhaps also captopril) seems to reduce the incidence of ventricular arrhythmias in the early phase of acute myocardial infarction. The effects on life-threatening arrhythmias, such as ventricular fibrillation, and on death can only be assessed in a much larger trial.

Early and late changes in left ventricular filling after acute myocardial infarction and the effect of infarct size.

To characterize the early (1 week) and late (6 weeks) changes in left ventricular (LV) filling pattern associated with acute myocardial infarction (AMI) 45 patients (mean age 65 +/- 2 years) were studied by Doppler echocardiography. Based on clinical criteria, patients were divided into those with large (group L; n = 12) and those with small (group S; n = 33) infarcts and then compared with 16 age-matched control subjects. The following parameters were calculated from the mitral velocity waveform: (1) peak early and peak atrial velocities and their integrals; (2) peak early to atrial velocity ratio and velocity integral ratio; and (3) the pressure half-time of the early wave. One week after AMI, group L showed a decreased atrial and increased early velocity, velocity ratio and integral ratio, whereas the pressure half-time of the early wave was shorter than that in group S and in control subjects. At 6 weeks group L showed a reduction in early velocity, early to atrial velocity ratio and integral ratio, whereas pressure half-time increased. When groups S and L were combined there was a good inverse correlation between pressure half-time and infarct size as measured by peak enzyme release (r = -0.64, p < 0.001). These data suggest that, depending on infarct size, patients exhibit a "restrictive" filling pattern early after the acute event. This is manifested by the greater proportion of filling occurring in early diastole, reflecting an overall increase in chamber stiffness. At 6 weeks, this pattern is less pronounced presumably due to the remodeling process.

Effects of mild physical activity, atenolol and the combination on ambulatory blood pressure in hypertensive subjects.

OBJECTIVE: To evaluate whether beta-blocker treatment could enhance the effect of a mild physical training programme upon blood pressure. DESIGN AND METHODS: In 12 hypertensive subjects (mean age: 40.3 years) a prospective randomized Latin square-design trial was performed with three treatments: physical training and placebo tablets; atenolol 50 mg once a day and inactivity; and physical training and atenolol 50 mg once a day. RESULTS: Training significantly increased maximal ventilatory oxygen consumption (VO2MAX), and there was a decrease in ambulatory diastolic blood pressure (DBP) which did not reach statistical significance. Atenolol alone significantly reduced ambulatory systolic blood pressure (SBP) and DBP. Atenolol alone did not reduce VO2MAX. The combination of training and atenolol resulted in an increase in VO2MAX compared with atenolol alone, but no additional significant fall in blood pressure. CONCLUSIONS: Atenolol did not enhance the effect of physical training upon blood pressure and had little if any effect upon the training-induced increase in exercise tolerance.

Comparison of the normal sinus node with seven types of rate responsive pacemaker during everyday activity.

The heart rate response of 59 patients aged 17-79 years implanted with seven different types of rate responsive pacemakers was evaluated during graded exercise treadmill testing and during standardised daily activities. The heart rate response in patients with pacemakers was compared with the chronotropic response in 20 healthy controls of similar age and sex distribution who performed identical protocols. All pacemaker types adequately simulated the control heart rate response during the graded exercise treadmill test except during the early stages of exercise. However, during everyday activities, the response of ventricular rate responsive (VVIR) pacemakers was varied. Activity sensing systems rapidly overresponded to staircase descent, to changes in walking speed, and to suitcase lifting with the pacemaker arm, and these systems did not respond to mental stress. "Physiological" sensors (QT and minute ventilation units) responded slowly to rapid changes in physiological demand. The QT pacemaker patients did respond to mental stress but showed a paradoxical increase in rate during the recovery phases of burst exercise protocols such as staircase ascent/descent and walking deceleration. Dual chamber pacemakers in VDD, DDD, and DDDR modes most closely simulated the normal chronotropic response during everyday activities. Graded exercise treadmill testing, in isolation, may not be the best way to asses or program the heart rate response in patients with the heart rate adaptive pacemakers because changes in heart rate during everyday activities may deviate considerably from the normal sinus response despite satisfactory simulation of the normal chronotropic response during treadmill testing.

Angiographic morphology of recurrent stenoses after percutaneous transluminal coronary angioplasty: are lesions longer at restenosis?

Angiographic morphology was analysed in 32 patients who developed restenosis after initially successful coronary angioplasty. The mean minimal luminal diameter of the dilated coronary segments increased from 0.9 mm to 2.3 mm after dilatation, but decreased to 0.9 mm at restenosis. The reference diameter was unchanged after dilatation and at restenosis. Mean stenosis length before the initial angioplasty was 7.0 mm but at the repeat procedure had increased to 8.7 mm (mean increase 1.7 mm, 95% confidence interval 0.6 to 2.8 mm, p less than 0.01). There were no significant differences in mean trans-stenotic pressure gradient and mean eccentricity ratio between the initial and repeat angioplasty procedures. In individual patients the changes in stenosis morphology were unpredictable, but overall stenoses tended to be longer at restenosis. In some patients stenosis length increased by several millimetres but the success rate of repeat angioplasty was high and the clinical importance of the changes in stenosis morphology are uncertain.

Quantitative analysis of contribution of rate response in three different ventricular rate responsive pacemakers during out of hospital activity.

The contribution of rate response provided by three different types of rate responsive pacemaker (Sensolog, Meta, and Vitatron TX) was assessed in 25 patients during out of hospital activity. Pacemakers were optimally programmed and full disclosure 24-hour Holter ECG recordings were obtained during everyday activities. Close visual analysis of these tracings revealed that rate response is active for less than 15% of the 24-hour study period with high rate response (paced rate above 100 beats/min) for just 5% of the day showing peak activation between 1600 and 2000 hours. Low rate response (paced rate below 100 beats/min but 5 beats above base rate) was maximal between 0800 hours and midday and comprised 10% of all heart beats during the study period. Thirty percent of study patients were nonpacemaker dependent and rate response in these subjects was significantly (P less than 0.001) less active between 0800 hours and midday than in pacemaker dependent patients though it was equivalent at all other times. Nonpacemaker dependent patients achieved natural sinus response in the morning and tended to rely on pacemaker supplied rate response in the latter part of the day.

Effects of coronary artery surgery on left ventricular performance, segmental wall movement, and exertional ischaemia.

The effects of coronary artery surgery on left ventricular performance were assessed serially by echocardiography and treadmill exercise testing in 54 patients. Patients were assessed one day before operation and again before patients left hospital (mean 10 days after operation) and one month and six months after operation. At the predischarge assessment, 41 (77%) patients showed new abnormalities of left ventricular segmental wall movement, chiefly anteroseptal hypokinesia with hyperkinesia of the posterolateral segment. Although there were no significant changes in anteroseptal wall thickening after operation, there was a significant increase in posterior wall thickening at all postoperative assessments. The frequency of this abnormality decreased progressively after operation; it persisted in 19 (35%) patients at six months. Left ventricular fractional shortening decreased after operation and at one month was significantly less than before operation. There were no significant changes in left ventricular diastolic diameter during the study. Haemodynamic function during exercise, the duration of exercise, and features of reversible myocardial ischaemia all improved progressively and significantly after coronary artery surgery. Abnormalities in left ventricular segmental wall movement and thickening commonly develop early after coronary artery surgery but tend to resolve by six months and do not seem to impair left ventricular contractility at rest or exercise performance and haemodynamic function. Recognition of these echocardiographic changes may be clinically important in the assessment of patients after cardiac surgery.